Mark Connors
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View article: Inclusion of a retroviral protease enhances the immunogenicity of VLP-forming mRNA vaccines against HIV-1 or SARS-CoV-2 in mice
Inclusion of a retroviral protease enhances the immunogenicity of VLP-forming mRNA vaccines against HIV-1 or SARS-CoV-2 in mice Open
Messenger RNA (mRNA) has emerged as a highly effective and versatile platform for vaccine delivery. We previously designed a virus-like particle (VLP)–forming env-gag mRNA vaccine against human immunodeficiency virus–1 (HIV-1) that elicite…
View article: Antigen Dose and Persistence Contribute to Induction of a Durable HIV-1-Specific Neutralizing Antibody Response
Antigen Dose and Persistence Contribute to Induction of a Durable HIV-1-Specific Neutralizing Antibody Response Open
The immunogenicity of HIV-1 Env glycoprotein (Env) is limited in part by its structural instability and extensive glycan shielding and is likely the greatest obstacle to an HIV-1 vaccine. Stabilized Env trimers can elicit serum neutralizin…
View article: A multidonor class of highly glycan-dependent HIV-1 gp120-gp41 interface-targeting broadly neutralizing antibodies
A multidonor class of highly glycan-dependent HIV-1 gp120-gp41 interface-targeting broadly neutralizing antibodies Open
Antibodies that target the gp120-gp41 interface of the HIV-1 envelope (Env) trimer comprise a commonly elicited category of broadly neutralizing antibodies (bNAbs). Here, we isolate and characterize VRC44, a bNAb lineage with up to 52% neu…
View article: Immune perturbations in HIV-1–infected individuals who make broadly neutralizing antibodies
Immune perturbations in HIV-1–infected individuals who make broadly neutralizing antibodies Open
Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. bnAbs occur in some HIV-1–infected individuals and frequently have characteristics of autoantibodies. We have studied cohorts of HIV-1–infected in…
View article: RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses
RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses Open
HIV-1 broadly neutralizing antibodies (bnAbs) are difficult to induce with vaccines but are generated in ∼50% of HIV-1-infected individuals. Understanding the molecular mechanisms of host control of bnAb induction is critical to vaccine de…
View article: Application of B cell immortalization for the isolation of antibodies and B cell clones from vaccine and infection settings
Application of B cell immortalization for the isolation of antibodies and B cell clones from vaccine and infection settings Open
The isolation and characterization of neutralizing antibodies from infection and vaccine settings informs future vaccine design, and methodologies that streamline the isolation of antibodies and the generation of B cell clones are of great…
View article: A trispecific Ab directed to HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections
A trispecific Ab directed to HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections Open
The main barrier to HIV virus eradication is the presence of long-lived HIV-1 that persists in latent reservoirs. Current efforts have focused on HIV cure interventions that “shock and kill” virally infected cells to purge the latent pool.…
View article: Application of B cell immortalization for the isolation of antibodies and B cell clones from vaccine and infection settings
Application of B cell immortalization for the isolation of antibodies and B cell clones from vaccine and infection settings Open
The isolation and characterization of neutralizing antibodies from infection and vaccine settings will inform future vaccine design, and methodologies that streamline the isolation of antibodies and the generation of B cell clones are of g…
View article: High-Throughput B Cell Epitope Determination by Next-Generation Sequencing
High-Throughput B Cell Epitope Determination by Next-Generation Sequencing Open
Development of novel technologies for the discovery of human monoclonal antibodies has proven invaluable in the fight against infectious diseases. Among the diverse antibody repertoires elicited by infection or vaccination, often only rare…
View article: Structures of HIV-1 Neutralizing Antibody 10E8 Delineate the Mechanistic Basis of Its Multi-Peak Behavior on Size-Exclusion Chromatography
Structures of HIV-1 Neutralizing Antibody 10E8 Delineate the Mechanistic Basis of Its Multi-Peak Behavior on Size-Exclusion Chromatography Open
Antibody 10E8 is capable of effectively neutralizing HIV through its recognition of the membrane-proximal external region (MPER), and a suitably optimized version of 10E8 might have utility in HIV therapy and prophylaxis. However, 10E8 dis…
View article: Functional Anatomy of the Trimer Apex Reveals Key Hydrophobic Constraints That Maintain the HIV-1 Envelope Spike in a Closed State
Functional Anatomy of the Trimer Apex Reveals Key Hydrophobic Constraints That Maintain the HIV-1 Envelope Spike in a Closed State Open
Elucidating the structure and function of the HIV-1 outer envelope proteins is critical for the design of an effective vaccine. Despite the availability of many high-resolution structures, key functional correlates in the envelope trimer r…
View article: Evaluating a New Class of AKT/mTOR Activators for HIV Latency-Reversing Activity <i>Ex Vivo</i> and <i>In Vivo</i>
Evaluating a New Class of AKT/mTOR Activators for HIV Latency-Reversing Activity <i>Ex Vivo</i> and <i>In Vivo</i> Open
If combined with immune therapeutics, latency-reversing agents (LRAs) have the potential to reduce the size of the reservoir sufficiently that an engineered immune response can control the virus in the absence of antiretroviral therapy. We…
View article: A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity
A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity Open
BACKGROUNDTo understand the features of a replicating vaccine that might drive potent and durable immune responses to transgene-encoded antigens, we tested a replication-competent adenovirus type 4 encoding influenza virus H5 HA (Ad4-H5-Vt…
View article: SARS-CoV-2 Vaccines: Much Accomplished, Much to Learn
SARS-CoV-2 Vaccines: Much Accomplished, Much to Learn Open
As COVID vaccines roll out, internists and other health care providers are being turned to as trusted sources of information for patients and communities. Here, experts from NIAID outline the current state of knowledge regarding such vacci…
View article: Lost in Translation: Lack of CD4 Expression due to a Novel Genetic Defect
Lost in Translation: Lack of CD4 Expression due to a Novel Genetic Defect Open
CD4 expression identifies a subset of mature T cells primarily assisting the germinal center reaction and contributing to CD8+ T-cell and B-cell activation, functions, and longevity. Herein, we present a family in which a novel variant dis…
View article: Prolonged Posttreatment Virologic Control and Complete Seroreversion After Advanced Human Immunodeficiency Virus-1 Infection
Prolonged Posttreatment Virologic Control and Complete Seroreversion After Advanced Human Immunodeficiency Virus-1 Infection Open
Background Possible human immunodeficiency virus (HIV)-1 clearance has rarely been reported. In this study, we describe a unique case of an HIV-positive, combination antiretroviral therapy (cART)-experienced woman with prior acquired immun…
View article: Structure and immune recognition of trimeric pre-fusion HIV-1 Env
Structure and immune recognition of trimeric pre-fusion HIV-1 Env Open
The HIV-1-envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a postfusion s…
View article: Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors
Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors Open
The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated…
View article: Antigenic Restimulation of Virus-Specific Memory CD8<sup>+</sup>T Cells Requires Days of Lytic Protein Accumulation for Maximal Cytotoxic Capacity
Antigenic Restimulation of Virus-Specific Memory CD8<sup>+</sup>T Cells Requires Days of Lytic Protein Accumulation for Maximal Cytotoxic Capacity Open
Antigen-specific CD8 + T cells play a major role in controlling most virus infections, primarily by perforin (PRF)- and granzyme B (GrB)-mediated apoptosis. There is considerable controversy regarding whether PRF is constitutively expresse…
View article: Toll-like receptor 7-adapter complex modulates interferon-α production in HIV-stimulated plasmacytoid dendritic cells
Toll-like receptor 7-adapter complex modulates interferon-α production in HIV-stimulated plasmacytoid dendritic cells Open
Plasmacytoid dendritic cells (PDCs) and their production of interferon-alpha (IFN-α) are believed to play an important role in human immunodeficiency virus, type I (HIV-1) pathogenesis. PDCs produce IFN-α and other proinflammatory cytokine…
View article: Adoptive lymphocyte transfer to an HIV-infected progressor from an elite controller
Adoptive lymphocyte transfer to an HIV-infected progressor from an elite controller Open
BACKGROUNDHIV-infected patients with poor virologic control and multidrug-resistant virus have limited therapeutic options. The current study was undertaken to evaluate the safety, immunologic effects, and antiviral activity of peripheral …
View article: Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation
Structural Constraints at the Trimer Apex Stabilize the HIV-1 Envelope in a Closed, Antibody-Protected Conformation Open
The extraordinary ability of human immunodeficiency virus type 1 (HIV-1) to evade host immunity represents a major obstacle to the development of a protective vaccine. Thus, elucidating the mechanisms whereby HIV-1 protects its external en…
View article: MAdCAM costimulation through Integrin-α4β7 promotes HIV replication
MAdCAM costimulation through Integrin-α4β7 promotes HIV replication Open
Human gut-associated lymphoid tissues (GALT) play a key role in the acute phase of HIV infection. The propensity of HIV to replicate in these tissues, however, is not fully understood. Access and migration of naive and memory CD4+ T cells …
View article: Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections
Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections Open
There is great interest in passive transfer of broadly neutralizing antibodies (bnAbs) and engineered bispecific antibodies (Abs) for prevention of HIV-1 infections due to their in vitro neutralization breadth and potency against global is…